U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

1 | Page

Guidelines for Autogenous Biologics 

1. Purpose and Background 

 

This memorandum describes the procedures and guidelines for interpreting the 

requirements for autogenous biologics at title 9, Code of Federal Regulations(9 CFR), 

sections 113.113, 113.3(b)(8), and the administrative terminology in section 101.2.

 

The Animal and Plant Health Inspection Service (APHIS) published the Standard 

Requirement for Autogenous Biologics in the Federal Register on April 3, 2002; the 

requirement became effective May 3, 2002. The Director, Center for Veterinary Biologics, 

Inspection and Compliance (CVB-IC), is authorized to make all decisions relating to the 

discretionary authorities assigned to the Administrator in 9 CFR 113.113, except 

113.113(c)(2)(iv), which requires approval by the CVB Policy Evaluation and Licensing 

(PEL) Director. 

Pursuant to the Congressional Review Act (5 U.S.C. § 801 et seq.), the Office of 

Information and Regulatory Affairs designated this [action] as a non-major rule, as 

defined by 5 U.S.C. § 804(2).

 

2. Document Status 

 

A. Issue Date: 11/22/2021 

 

B. This document replaces VSM 800.69, dated September 26, 2016. 

 

3. Reason for Reissuance 

 

CVB is reissuing this memorandum to:

• Inform licensees that autogenous isolates may be used for sixty (60) months 

without requesting permission fromCVB-PEL and will be evaluated for use beyond 

sixty (60) months by CVB-PEL without the need to conduct an immunogenicity 

study.

• Include distribution of autogenous products to third-party cold storage facilities 

prior to final herd distribution.

• Address requirements for approval of the production of autogenous products for 

export only.

• Notify licensees that shipments to adjacent and nonadjacent herds will be 

permitted, provided the information cited in 9 CFR 113.113(a)(2) and (3) is on file 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

2 | Page

with the licensee prior to the shipment of an autogenous product for use in a herd 

other than the herd of origin. 

4. Authority and References 

 

A. Authorities 

• 9 CFR 101 

• 9 CFR 113 

• 9 CFR 114 

• 9 CFR 116 

 

B. References 

• VSM 800.53, Release of Biological Products

• VSM 800.56, Disposal of Unsatisfactory and Undesirable Materials

• VSM 800.59, Veterinary Biological Product Samples

• VSM 800.65, Eggs and Chickens for Production of Veterinary Biological Products 

• VSM 800.85, Avian Influenza Vaccine 

• VSM 800.103, Reissuance of Product Licenses for Autogenous Products and 

Guidance Concerning Restrictions on the Production and Use of Veterinary 

Biologics

• VSM 800.109, Master Seed and Master Cell Stock Testing Report Submission 

 

5. Audience 

VS employees and members of the biologics industry. 

6. Guidance 

A. Approval of Nonveterinarian Specialist

9 CFR 113.113 allows an autogenous biologic to be prepared for use by a person of 

specialized expertise other than a veterinarian in special situations if approved by the 

Administrator. CVB-IC uses professional judgment in determining whether the person 

has the appropriate expertise to administer the product and deal with possible 

medical problems associated with use of an autogenous biologic. Communicate the 

following information to CVB-IC when requesting approval to prepare an autogenous 

biologic for use by a nonveterinarian:

1. Identification. Name and qualifications (e.g., training, role in diagnosing the 

disease condition) of the nonveterinarian.

2. Justification. Description of the special situation (e.g., animal species involved, 

location, disease condition[s]).
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

3 | Page

B. Determination of Date of Isolation

9 CFR 113.113(a)(4)states that the microorganism used for the production of an 

autogenous biologic may not be older than fifteen (15) months from the date of 

isolation or twelve (12) months from the date of harvest of the first serial of product 

produced from the microorganism(s), whichever comes first. This verbiage has 

historically caused confusion regarding the interpretation of the date of isolation and 

the concomitant initial isolate dating. For purposes of streamlining and clarifying the 

initial isolate dating period, all isolates may be used for an initial dating period of 

fifteen (15) months from the date of harvest of the first serial of product produced 

from the microorganism(s). 

C. Cells Used for Production 

1. Primary Cells. These should satisfy the requirements set forth in 9 CFR 113.51 and 

VSM 800.65 (if Specific Pathogen Free eggs are used). The appropriate citations 

should be included in the Outline of Production (Outline).

2. Cell Lines. These should satisfy the requirements prescribed in 9 CFR 113.52 and 

VSM 800.109 and be identified in the filed Outline. Since cell lines can be used to 

produce products for multiple animal species, the Outline must list the species for 

which the cell line is approved.

D. Extension on Use of Autogenous Isolate

9 CFR 113.113(a)(4) allows extended use of an isolate beyond fifteen (15) months 

from the date of isolation; however, this original dating period for isolate usage does 

not have any particular basis in fact, and, as noted in Section 6.B., has historically

been a source of confusion. Therefore, extensions of isolate usage to sixty (60)

months from the date of harvest of the first serial of product produced from the 

microorganism(s) will be permitted when requested by the attending veterinarian or 

nonveterinary specialist responsible for assessing the health needs of the herd of 

origin. Documentation of the continued need for use of the isolate does not require 

submission to CVB; however, the justification should be maintained on file for CVB’s

review upon inspection. CVB-PEL will evaluate extensions for isolate use beyond sixty 

(60) months. Extension requests must include the following information:

1. Assessment of Continued Involvement. A current assessment of the continued 

involvement of the originally isolated microorganism(s) with disease in the herd, 

including diagnostic work done to support this assessment.

2. Documentation of Satisfactory Performance. Provide documentation from the 

attending veterinarian or nonveterinary specialist to support that the previous 

use of the autogenous biologic was beneficial. In addition, provide the number of 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

4 | Page

doses administered and an assessment of any and all adverse events associated 

with the use of the biologic along with the request for extension of isolate usage 

beyond sixty (60) months. 

3. Inactivation kinetics. Review of inactivation procedures for products propagated 

in a manner susceptible to the introduction of viral contamination. To ensure the 

safety of isolate usage, inactivation methods used for the isolates being extended 

must demonstrate the ability to completely inactivate possible “worst case 

scenario” viral contaminants. This requirement will be for products grown in cell 

culture, eggs, or other methods capable of introducing viral contaminants, and 

will only apply to limited bacterial products such as those propagated in cells. The 

inactivation study must demonstrate complete inactivation of the proposed 

species-matched viral isolate at a level of 105 TCID50/ml. 

a. For autogenous swine products, the surrogate contaminating virus is porcine 

circovirus. 

b. For autogenous poultry products, the surrogate contaminating virus is chicken 

anemia virus.

c. For autogenous bovine products, the surrogate contaminating virus is bovine 

parvovirus. 

d. For autogenous products used in species other than swine, poultry, or 

bovines, firms could use one of the listed viruses, or propose an alternative 

for CVB consideration. 

The inactivation study must be conducted in a manner acceptable to CVB. Submit

protocols to CVB for review prior to initiating the studies. Approved studies must 

be on file for the autogenous license under which the isolate will be used. The 

study must be cited in the approved Outline of Production associated with the 

isolate usage. In cases where more than one inactivation method is allowed under 

the Outline of Production, only an inactivation method supported by the data 

outlined in this Section may be used on extended use isolates. These studies are 

one-time-only requirements and may be conducted preemptively and 

independently of any need for extended isolate usage. Firms with approved 

inactivation studies currently on file with CVB in their autogenous product 

Outlines should check with CVB to see if those studies will be sufficient to meet 

this requirement for the intended purpose of isolate extension.

4. History of Product. Date and place of isolation of microorganism(s) and date of 

harvest of first serial.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

5 | Page

5. Veterinarian/Client/Patient Relationship. Licensees are responsible for 

certification of a valid veterinarian/client/patient relationship by the veterinarian 

requesting the product, as defined by the American Veterinary Medical 

Association policy, “Principles of Veterinary Medical Ethics.” For the approved 

nonveterinarian specialist, supply equivalent information for CVB’s evaluation.

E. Disposition of Outdated Isolates 

Microorganisms used to prepare autogenous biologics shall not be maintained in a 

licensed establishment beyond the time authorized for use in production. Handle 

outdated isolates in accordance with 9 CFR 114.15 and VSM 800.56. Maintain records 

of the disposition of isolates as provided in 9 CFR 116. 

F. Definition of “First Serial” 

A serial is considered a “first serial” if it is the first serial of autogenous biologic 

produced (i.e., prepared and eligible for shipment to the customer) from a new 

isolate or isolates, or if the first batch of autogenous culture produced from a new 

isolate is added to fractions produced from previously used isolates. 

1. Age of Isolation. The serial must not include any culture that is over the age limit. 

2. Removal of Isolates. Removing an isolate from a previous autogenous biologic 

formulation does not make the modified product a “first serial”; it is automatically 

a subsequent serial.

G. Reporting of Autogenous Biologics

1. First Serials. The first serial of an autogenous biologic produced from an 

unrestricted isolate (see VSMs 800.85 and 800.103 for antigens not authorized for 

production under an autogenous license) may be released for shipment by the 

firm on the basis of satisfactory results of third-day observations of tests, in 

accordance with 9 CFR 113.113(c)(1). 

Once testing is complete, but no longer than thirty (30) days from completion of 

testing, submit a test summary to CVB. Since the implementation of the National 

Centers for Animal Health (NCAH) Portal, use of the summary format has 

diminished and will no longer be used to report first serials.

2. Subsequent serials. All serials, other than the first serial, made from unrestricted 

organisms. Submit Veterinary Biologics Production and Test Report information 

(APHIS Form 2008) to CVB-IC for each subsequent serial of autogenous biologics. 

In lieu of the APHIS Form 2008, the information may be submitted through the 

NCAH Portal, if the manufacturer has the appropriate access. This information will 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

6 | Page

be reviewed and processed as outlined in VSM 800.53. Do not ship subsequent 

serials prior to approval from CVB-IC.

3. Serials produced with restricted microorganisms

a. To ensure that the use of autogenous veterinary biologics does not interfere 

with animal disease surveillance and/or control and eradication programs and 

does not pose other health risks, the use of certain microorganisms is 

restricted. See VSMs 800.85 and 800.103 for a list of restricted organisms. 

b. Do not produce autogenous biologics from restricted organisms without CVB 

approval.

c. All (first and subsequent) serials of autogenous biologics that contain 

restricted organisms are released by the standard procedure described in 

section 6.G.2. 

H. Definition of Serial Size and Sample Submission/Retention 

The number of final containers in a serial or subserial is determined by the number of 

containers in inventory for release (i.e., available for sale). Do not submit samples of 

first serials of autogenous products, regardless of serial size, to CVB unless requested. 

Submit samples of subsequent serials filled in >50 containers to CVB in accordance 

with 9 CFR 113.3(b)(8). 

1. Number of Samples to Select. Based on the number of containers produced, 

allocate samples as follows: 

a. For serials with <50 containers, the firm selects two (2) government reserve 

samples only. This applies to first serials and subsequent serials.

b. For first serials with >50 containers, the firm selects ten (10) government 

reserve samples only. After the autogenous summary has been returned to 

the manufacturer, two (2) government reserve samples must be retained.

c. For subsequent serials with >50 containers, select ten (10)samples; however, 

submit only two (2) samples to CVB and hold two (2) as government reserve 

samples. The remaining six (6) samples may be returned to inventory, based 

on VSM 800.59.

2. Sampling Procedures. Select samples of all autogenous biologics in accordance 

with 9 CFR 113.3(b)(8). The licensee or permittee must hold reserve samples in 

accordance with 9 CFR 113.113(e)(4)and submit them to CVB only when 

requested.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

7 | Page

I. Retesting of Autogenous Serials 

First serials shipped after the third day of observation of purity test cultures and of 

safety test animals must be immediately recalled in the event of an inconclusive or 

unsatisfactory test result. CVB-IC must be immediately notified in the event of a 

product recall. The serial may be retested to rule out technician error. The retest 

must be completed and satisfactory before the serial can be released for continued 

shipment. 

J. Shipment of Autogenous Products 

1. The licensee or permittee is permitted to ship the autogenous serial to the 

veterinarian or approved nonveterinarian specialist for whom the product was 

prepared. 

2. With appropriate documentation, autogenous serials may be shipped directly to 

an owner or a third-party cold storage distribution facility for final distribution if 

approved by the veterinarian or nonveterinarian specialist ordering the 

autogenous serial. In the case of the third-party cold storage facility, prior 

permission to use the storage facility must be received from CVB-IC on a one-time 

basis. Once approved, these cold storage facilities are considered subject to 

unannounced inspections as deemed necessary to ensure compliance with the 

autogenous product distribution regulations. However, the licensee or permittee 

is ultimately responsible for all third-party adherence to the regulatons and this 

privilege may revoked at any time based on cause. Finally, serial distribution 

records must be readily available or maintained by the licensee or permitee for 

CVB-IC review.

3. Shipments to adjacent and nonadjacent herds will be permitted, provided the 

information cited in 9 CFR 113.113(a)(2) and (3) is on file with the licensee before 

an autogenous product is shipped for use in a herd other than the herd of origin. 

4. For purposes of product distribution, the herd of origin includes all animals of the 

same species and under common ownership regardless of the physical location of 

the individual herds. Autogenous serials for distribution to the herd of origin as 

described above are exempt from the records required for adjacent or 

nonadjacent herds provided the autogenous manufacturer has an approved 

inactivation kinetics study (or studies) on file with CVB and cited in the approved 

Outline for the autogenous license under which the product was produced as 

described in Section 6.D.3. above. This requirement is independent of any issues 

related to isolate dating. Manufacturers choosing not to perform the cited 

inactivation kinetics studies will not be afforded this new regulatory flexibility for 

intrastate and interstate movement and distribution of autogenous products 
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

8 | Page

within the herd of origin, and must fulfill all the requirements historically required 

for adjacent and nonadjacent distribution of autogenous biologics as cited in 9 

CFR 113.113(a)(2) and (3).

K. Autogenous Products for Export Only Distribution 

Manufacturers with an autogenous license are allowed to produce autogenous 

products for export only purposes. 

1. Obtain a valid Organisms and Vector (Form 16-3) permit to import the organism.

2. Depending on the situation and country of origin, CVB may also request a risk 

analysis for importation. 

3. With CVB approval, the isolate can be moved into the production facility. 

4. Autogenous products containing isolates originating from outside the United 

States are not eligible for use or distribution within the United States regardless 

of any potential epidemiological link with the foreign herd of origin. These 

autogenous products are only eligible for “export only” distribution.

5. The manufacturer’s internal records should clearly document this distribution 

restriction. 

6. Limitations on the organisms eligible for autogenous products are the same as for 

domestic products.

7. Short Guide to Autogenous Biologics 

A. Limit on Use of an Isolate 

1. The autogenous isolate may be used for fifteen (15) months from the date of 

harvest of the first serial of product produced from the microorganism(s).

2. Extended use of isolates to sixty (60) months from the date of harvest of the first 

serial of product produced from the microorganism(s) will be permitted when 

requested by the attending veterinarian or nonveterinary specialist. No approval 

from CVB is required for this extension, but records must document an ongoing 

need.

3. CVB-PEL evaluates extensions for use beyond sixty (60) months. Extension 

requests must include the information prescribed in 9 CFR 113.113(a)(4) as 

further clarified in this Memorandum.

4. Disposition of Outdated Isolates. All outdated isolates shall be handled in 

accordance with 9 CFR 114.15 and VSM 800.56. Maintain records of the 

disposition of isolates as provided in 9 CFR 116.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

9 | Page

B. Permissible Cells 

Tested primary cells or approved cell lines may be used in production, as indicated in 

the Outline. 

C. First Serial 

1. A first serial may be shipped after three (3) days of satisfactory testing.

2. CVB does not require samples of first serials. 

3. Firms should recall serials if tests are inconclusive or unsatisfactory.

4. Submit APHIS Form 2008 to CVB-IC, as listed in 6.G.1 of this memorandum,within 

thirty (30) days of testing completion. NCAH Portal submission is also acceptable.

5. Identification of the organism should be sufficient to determine it as the causative 

agent.

D. Second and Subsequent Serials

1. Second and subsequent serials must be tested under the general requirements in 

9 CFR 113.100 or 113.200 to include purity, safety, and identification (genus and 

species for bacteria; family for virus) with the exception that poultry products 

must be safety tested in poultry using the format specified in 9 CFR 113.116(b)

and 113.117(b). All killed virus vaccines (except for poultry vaccines) shall be 

safety tested in guinea pigs or mice. However, products for use in fish or other 

aquatic species, or reptiles, are exempt from this requirement and shall be tested 

in the species for which the product is recommended or an appropriate surrogate 

species as described and approved in the Outline of Production. Complete all 

testing and submit APHIS Form 2008 information to CVB-IC for release. Hard copy 

APHIS Form 2008 or NCAH Portal submission is acceptable.

2. Samples are submitted to CVB unless the serial is <50 containers. Confirmatory 

testing by CVB may occur. For serials of <50 containers, two reserve samples are 

held and may be requested by CVB.

3. APHIS must release the serial BEFORE it is shipped.

E. All Serials from Restricted Microorganisms 

1. CVB must approve production of autogenous biologics from organisms restricted 

in VSM 800.103.
U.S. DEPARTMENT OF AGRICULTURE 

Marketing and Regulatory Programs

Animal and Plant Health Inspection Service

Veterinary Services 

VS Memorandum (VSM) 800.69 

10 | Page

2. Submit APHIS Form 2008 for each serial (first and subsequent) of autogenous 

biologics produced from restricted microorganisms to CVB-IC. APHIS must release 

the serial before shipment. In lieu of the APHIS Form 2008, the information may 

be submitted through the NCAH Portal if employees at the manufacturer have 

received the appropriate access. 

8. Implementation/Applicability 

Updated policy in this memorandum is effective immediately.